Part I: The overall objective of this part of the proposal will be to assess in the dog and in man major hemodynamic effects of different cardiac pacing modes as a function of ischemia. Special emphasis will be placed on the definition of mechanisms by which these effects take place and the role of ischemia in altering quantitatively or qualitatively the effects of a given pacing mode. Part II: The objective of this portion of the proposal is to assess in the dog the potential protective effect of acidosis (versus alkalosis) during and after exposure of the myocardium to hypoxia or ischemia. Previous work has documented the depressant effect of acidosis on myocardial contractility and the diminished response of the myocardium to endogenous catecholamines during acidosis. Conversely, positive inotropic interventions in ischemic states have been shown to lead to both functional deterioration and further ischemic necrosis. The present study would attempt to clarify the role of hydrogen ion as a regulator of cardiac function in the presence of ischemia or hypoxia and to confirm or reject the postulate that acid production which accelerates during acute ischemia or hypoxia may actually protect against cell death. Part III: The principal objective of this portion of the proposal is to investigate in dogs the effects on cardiac performance of hemodilution with a crystalloid solution. Special emphasis will be placed on correlating changes in ventricular function with changes in the water content of the myocardium. Concepts to be derived from this study appear important to the conduct of cardiopulmonary bypass and physiological effects thereof in the clinical setting.